Introduction: The heavy, regular use of alcohol has been associated with significant morbidity and mortality, particularly in post-menopausal women. The consumption of high levels of alcohol has been associated with increased risk for breast, endometrial, and ovarian cancer. The risks associated with low to moderate alcohol consumption are much less clear. This may be due to differences in hormone replacement therapy or folic acid intake or to the difficulty associated with accurately assessing level of drinking. We hypothesize that high levels of alcohol use will be associated with a higher likelihood of developing breast, endometrial, and ovarian cancer and that folic acid intake will moderate the effect of alcohol on these cancers. Design: The Women's Health Initiative Observational Study cohort consists of 93,717 post-menopausal women who were enrolled between September 1993 until December 1998, nationwide. To date, there have been 1,999 incident cases of breast cancer, 253 cases of endometrial cancer, and 188 cases of ovarian cancer among the women enrolled in this study. Data regarding the use of alcohol, dietary folic acid, and the use of folic acid supplements was collected on each participant at baseline and again at a followup visit. We propose to conduct a secondary data analysis of the effect of alcohol consumption and folic acid intake on the risk of developing these hormone-related cancers. Conclusions: Breast cancer now ranks second in cancer deaths among United States' women and is a leading cause of morbidity. While the incidence of endometrial cancer is not as high, and because of early detection, mortality rates are low, endometrial cancer resulted in over 6,500 deaths in 2001. Ovarian cancer, though much less common, is associated with a very high mortality rate (approximately 50% for all stages) because it is often not detected until late stage. The Women's Health Initiative database provides a unique opportunity to explore the relationship of alcohol and folic acid intake with hormone-related cancers in post-menopausal women.